Prevalence and Predictors of Tuberculosis Coinfection among HIV-Seropositive Patients Attending the Aminu Kano Teaching Hospital, Northern Nigeria

Background: The HIV/AIDS epidemic has been accompanied by a severe epidemic of tuberculosis (TB), although the prevalence of coinfection is largely unknown, especially in developing countries, including Nigeria. The aim of this study was to determine the prevalence and predictors of TB coinfection among HIV-seropositive Nigerians. Methods: The case files of HIV/AIDS patients attending Aminu Kano Teaching Hospital, Nigeria from January to December 2006 were reviewed. Results: A total of 1320 HIV/AIDS patients had complete records and were reviewed, among which 138 (10.5%) were coinfected with TB (95% CI, 8.9% to 12.2%). Pulmonary TB was diagnosed in 103 (74.6%) patients, among whom only 18 (17.5%) were sputum-positive. Fifty (36.2%) coinfected patients had some type of extrapulmonary TB (EPTB); 15 had both pulmonary TB and EPTB. Among the 35 patients with EPTB only, 20 (57.1%) had abdominal TB, 5 (14.3%) had TB adenitis, 5 (14.3%) had spinal TB, 3 (8.6%) were being monitored for tuberculous meningitis, and 1 (2.9%) each had renal TB and tuberculous adrenalitis. The highest prevalence of TB, 13.7% (n = 28), was seen among patients aged 41–50 years. TB coinfection was significantly associated with marital status, WHO clinical stage, and CD4 count. Marital status (OR, 2.1; 95% CI, 1.28–3.59; P = 0.04), WHO clinical stage at presentation (4.81; 1.42–8.34; P = 0.001), and baseline CD4 count (2.71; 1.51–6.21; P = 0.02) remained significant predictors after adjustment for confounding. Conclusions: The moderately high prevalence of TB among HIV-seropositive patients underscores the urgent need for strategies that lead to rapid identification and treatment of coinfection with active or latent TB

Intersection of phosphate transport, oxidative stress and TOR signalling in Candida albicans virulence

Phosphate is an essential macronutrient required for cell growth and division. Pho84 is the major high-affinity cell-surface phosphate importer of Saccharomyces cerevisiae and a crucial element in the phosphate homeostatic system of this model yeast. We found that loss of Candida albicans Pho84 attenuated virulence in Drosophila and murine oropharyngeal and disseminated models of invasive infection, and conferred hypersensitivity to neutrophil killing. Susceptibility of cells lacking Pho84 to neutrophil attack depended on reactive oxygen species (ROS): pho84-/- cells were no more susceptible than wild type C. albicans to neutrophils from a patient with chronic granulomatous disease, or to those whose oxidative burst was pharmacologically inhibited or neutralized. pho84-/- mutants hyperactivated oxidative stress signalling. They accumulated intracellular ROS in the absence of extrinsic oxidative stress, in high as well as low ambient phosphate conditions. ROS accumulation correlated with diminished levels of the unique superoxide dismutase Sod3 in pho84-/- cells, while SOD3 overexpression from a conditional promoter substantially restored these cells’ oxidative stress resistance in vitro. Repression of SOD3 expression sharply increased their oxidative stress hypersensitivity. Neither of these oxidative stress management effects of manipulating SOD3 transcription was observed in PHO84 wild type cells. Sod3 levels were not the only factor driving oxidative stress effects on pho84-/- cells, though, because overexpressing SOD3 did not ameliorate these cells’ hypersensitivity to neutrophil killing ex vivo, indicating Pho84 has further roles in oxidative stress resistance and virulence. Measurement of cellular metal concentrations demonstrated that diminished Sod3 expression was not due to decreased import of its metal cofactor manganese, as predicted from the function of S. cerevisiae Pho84 as a low-affinity manganese transporter. Instead of a role of Pho84 in metal transport, we found its role in TORC1 activation to impact oxidative stress management: overexpression of the TORC1-activating GTPase Gtr1 relieved the Sod3 deficit and ROS excess in pho84-/- null mutant cells, though it did not suppress their hypersensitivity to neutrophil killing or hyphal growth defect. Pharmacologic inhibition of Pho84 by small molecules including the FDA-approved drug foscarnet also induced ROS accumulation. Inhibiting Pho84 could hence support host defenses by sensitizing C. albicans to oxidative stress

Reducing complication rates and hospital readmissions while revising the enhanced recovery after bariatric surgery (ERABS) protocol

Background: To optimize the postoperative phase following bariatric surgery, the enhanced recovery after bariatric surgery pathway (ERABS) has been developed. The aim of ERABS is to create a care path that is as safe, efficient and patient-friendly as possible. Continuous evaluation and optimization of ERABS are important to ensure a safe treatment path and may result in better outcomes. The objective of this study was to compare the clinical outcomes of patients undergoing bariatric surgery over 2014–2017, during which the ERABS protocol was continuously evaluated and optimized. Methods: This is a retrospective cohort study. Data were collected from patients undergoing a primary Roux-en-Y gastric bypass or sleeve gastrectomy between January 2014 and December 2017. Outcomes were early complications, unplanned hospital revisits, readmissions, duration of surgery and length of hospital stay. Results: 2889 patients underwent a primary bariatric procedure in a single center. There was a significant decrease in minor complications over the years from 7.0 to 1.9% (p < 0.001). Hospital revisit rates decreased after 2015 (p < 0.001). Readmission rates decreased over time (p < 0.001). The mean duration of surgery decreased from 52 (in 2014) to 41 (in 2017) minutes (p < 0.001). Median length of hospital stay decreased from 1.8 to 1.5 days in 2015 (p = 0.002) and remained stable since. Conclusion: An improvement of the ERABS protocol was associated with a decrease in minor complication rates, number of unplanned hospital revisits and readmission rates after primary bariatric procedures